Lipidomic Analysis: From Archaea to Mammals.
Lipids are among the most important organic compounds found in all living cells, from primitive archaebacteria to flowering plants or mammalian cells. They form part of cell walls and constitute cell storage material. Their biosynthesis and metabolism play key roles in faraway topics such as biofuel production (third-generation biofuels produced by microorganisms, e.g. algae) and human diseases such as adrenoleukodystrophy, Zellweger syndrome, or Refsum disease. Current lipidomic analysis requires fast and accurate processing of samples and especially their characterization. Because the number of possible lipids and, more specifically, molecular species of lipids is of the order of hundreds to thousands, it is necessary to process huge amounts of data in a short time. There are two basic approaches to lipidomic analysis: shotgun and liquid chromatography-mass spectometry. Both methods have their pros and cons. This review deals with lipidomics not according to the type of ionization or the lipid classes analyzed but according to the types of samples (organisms) under study. Thus, it is divided into lipidomic analysis of archaebacteria, bacteria, yeast, fungi, algae, plants, and animals.


Germinated barley foodstuff increases fecal volume and butyrate production at relatively low doses and relieves constipation in humans.
Germinated barley foodstuff (GBF), derived from the aleurone layer, scutellum and germ of germinated barley, contains a large quantity of fermentable dietary fibers, especially hemicellulose. GBF was given to 9 healthy volunteers in a dose of 9 g of GBF per day for 10 consecutive days, and subsequently 18 g of GBF for another 10 days. As a control, no GBF was given for 3 days before administration of GBF (control period). Fecal weight, water content and short chain fatty acid content were measured before and during the last 3 days of each experimental period. Feeding of GBF significantly increased the fecal butyrate content as well as fecal weight at both dose-levels (9 and 18 g/day), compared with those during the control period. Daily administration of 9 g GBF induced the maximum level of defecation in humans. Relatively mild but chronic constipated volunteers (n = 16) were administered 9 g of GBF daily for 14 days. In this experiment, the condition of defecation (frequency, volume) was estimated by a questionnaire survey. GBF significantly improved defecation within a short period without severe adverse effects. No major abnormalities in laboratory findings were found in hematologic and urinary analyses. In conclusion, daily administration of 9 g GBF was effective for improving defecation in healthy but constipated humans. GBF is a highly safe and effective foodstuff for improving defecation.


Meta-synthesis exploring barriers to health seeking behaviour among Malaysian breast cancer patients.
Barriers to health seeking constitute a challenging issue in the treatment of breast cancer. The current meta- synthesis aimed to explore common barriers to health seeking among Malaysian breast cancer patients. From the systematic search, nine studies were found meeting the inclusion criteria. Data extraction revealed that health behavior towards breast cancer among Malaysia women was influenced by knowledge, psychological, sociocultural and medical system factors. In terms of knowledge, most of the Malaysian patients were observed to have cursory information and the reliance on the information provided by media was limiting. Among psychological factors, stress and sense of denial were some of the common factors leading to delay in treatment seeking. Family member's advice, cultural beliefs towards traditional care were some of the common sociocultural factors hindering immediate access to advanced medical diagnosis and care. Lastly, the delay in referral was one of the most common health system-related problems highlighted in most of the studies. In conclusion, there is an immediate need to improve the knowledge and understanding of Malaysian women towards breast cancer. Mass media should liaise with the cancer specialists to disseminate accurate and up-to-date information for the readers and audience, helping in modification of cultural beliefs that hinder timing health seeking. However, such intervention will not improve or rectify the health system related barriers to treatment seeking. Therefore, there is an immediate need for resource adjustment and training programs among health professional to improve their competency and professionalism required to develop an efficient health system.


Real-time heart rate variability analysis as a means of hypercapnia detection.
We hypothesized that heart rate variability (HRV) can be used as a physiological monitor of exposures to hypercapnia. HRV was analyzed in 15 male subjects breathing air and then air plus 4%, 5% or 6% carbon dioxide (CO2). A progressive elevation in randomness of HRV best depicted as a divergence of data on Poincar é plots of self-similarity occurred as CO2 increased, and resolved when returning sd to ambient conditions. Results indicate that HRV may be useful as a prompt (⟨ 2 minute) early warning of hypercapnia that occurs prior to overt symptomatology.


Spontaneous abortions and malformations in the offspring of nurses exposed to anaesthetic gases, cytostatic drugs, and other potential hazards in hospitals, based on registered information of outcome.
Nurses working in selected departments of general hospitals in Finland were collected from a central register on health personnel in Finland. Using the Hospital Discharge Register and the Register of Congenital Malformations, case nurses were selected who had had a spontaneous abortion (N = 217) or a malformed child (N = 46) between the years 1973 and 1979. Controls consisted of three nurses who had had a normal birth; the control nurses were matched for age and hospital of employment. Information on exposure in the first trimester of pregnancy was sought through the head nurses of the hospitals. No significant increase in risk of spontaneous abortion or of malformation was observed after exposure to anaesthetic gases (odds ratio for spontaneous abortion 1.2), sterilising gases and soaps, or x-rays. Handling of cytostatic drugs did not affect the frequency of spontaneous abortion but was associated with malformations in the offspring. The odds ratio, based on eight cases, was 4.7 (p = 0.02) when the logistic model was adopted. The results suggest that the exposures investigated, other than cytostatic drugs, do not cause a strong reproductive risk. Further studies are needed, particularly on cytostatic drugs.


Clinical and computed tomography analysis of intracerebral haemorrhage.
The clinical records and computed tomography scans of 50 consecutive patients with intracerebral haemorrhage (ICH) were analysed. Putaminal (48%) and thalamic (16%) ICH comprised the largest group, followed by cerebellar haemorrhage (12%). Intraventricular haemorrhage was observed in 14 cases, a majority being secondary to parenchymal haemorrhage. Hypertension remained the most important risk factor, occurring in 64% of the whole group and 83% of those with putaminal ICH. No predisposing factors for the haemorrhage were identified in 28% of patients. Twenty-seven patients were comatose; the incidence of coma in association with intraventricular haemorrhage was 79%. At the third week, 13 patients had died, a mortality rate of 26%.


Localization of ribosomal protein L5 mRNA in myoplasm during ascidian development.
We have isolated and characterized the cDNA clone ScYC26a from the ascidian Styela clava based on its relationship to the non-coding yellow crescent (YC) RNA. The ScYC26a mRNA has a long 5' non-coding sequence that is complementary to YC RNA. The deduced amino acid sequence indicates that ScYC26a encodes the ribosomal protein L5. The ScYC26a mRNA is probably encoded by a single copy gene, which shares genomic DNA restriction fragments with the gene encoding YC RNA, suggesting that the ScYC26a and YC genes are closely linked in the S. clava genome. Northern blot hybridization showed that S. clava eggs and embryos contain maternal ScYC26a mRNA and that zygotic ScYC26a transcripts do not accumulate until after metamorphosis. In situ hybridization showed that maternal ScYC26a mRNA is localized in the myoplasm and is segregated primarily to the muscle cell lineages during embryogenesis. The interaction of YC and ScYC26a transcripts may be involved in translational control or localization of L5 mRNA in the myoplasm.


Immunologic characterization of a cloned fragment containing the species-specific epitope from the major outer membrane protein of Chlamydia trachomatis.
A 183-bp fragment encoding variable domain IV (VD IV) of Chlamydia trachomatis serovar B major outer membrane protein (MOMP) (amino acids 273 to 333) and containing the species-specific epitope was cloned and expressed in Escherichia coli as a fusion protein with Schistosoma japonicum glutathione S-transferase (GST-VD IV). The fusion protein was affinity purified under nondenaturing conditions and used to immunize rabbits. Antisera were characterized by microimmunofluorescence, immunoblot, dot blot, peptide enzyme-linked immunosorbent, and in vitro neutralization assays. Antisera recognized MOMP from all 12 tested serovars of C. trachomatis but not from Chlamydia psittaci. In a dot blot assay, antisera bound to elementary bodies of serovars B, D, E, L2, and K in a strong fashion and to elementary bodies of serovars F, G, A, and H in a weak fashion but not to elementary bodies of serovars C, J, and I. High-resolution peptide mapping with synthetic overlapping serovar B MOMP peptides in a solid-phase enzyme-linked immunosorbent assay showed that immunization with GST-VD IV produced a serologic response that closely mimicked the response produced with purified serovar B elementary bodies. Antipeptide antibodies with strong binding to species- and subspecies-specific epitopes were elicited. Antisera were able to neutralize only those C. trachomatis serovars that bound antibodies in the dot blot assay. These results suggest that antigenic fragments from VD IV containing the species-specific epitope may be useful in the construction of a chlamydial vaccine for some but not all C. trachomatis serovars.


The ross procedure for replacement of the bicuspid aortic valve: mid-term results from 55 consecutive cases.
A congenitally dysfunctioning bicuspid aortic valve may require surgical treatment in children and young adults. This retrospective study evaluated mid-term clinical results obtained with the Ross procedure in this patient group. Between July 1994 and December 2000, 55 patients (48 males, seven females; mean age 27+/-10 years; range: 7-49 years) underwent replacement of a diseased bicuspid aortic valve (stenosis in six cases (11%); insufficiency in 36 (65%); mixed lesion in 13 (24%)) with a pulmonary autograft. Mean NYHA functional class was 1.7. Five patients (9%) had healed endocarditis and six (11%) had previous cardiac surgery. The autograft was inserted as a subcoronary implant in two cases (4%), as a root in 40 (73%), and as a cylinder in 13 (23%). The right ventricular outflow tract was reconstructed with a cryopreserved pulmonary homograft in all cases. Mean cardiopulmonary bypass and aortic cross-clamp times were 207+/-34 min and 162+/-18 min, respectively. No early or late deaths had occurred at a mean follow up of 31+/-19 months. Two patients (4%) were re-explored for bleeding. Four patients (7%) experienced intraoperative coronary complications which resolved without sequelae. Two-dimensional echocardiographic evaluation of neoaortic valve competence at six months revealed no evidence of aortic valve regurgitation in 46 patients (84%), trivial regurgitation in seven (13%), mild regurgitation in one patient (2%), and moderate regurgitation in one patient. The latter patient (subcoronary implant) required reoperation. At six months, the degree of regression of left ventricular mass compared (versus preoperative) was 34+/-13% (p <0.05). Three patients (5%) showed mild dilatation (>4 cm) of the neoaortic root after two years follow up. All patients are currently asymptomatic, in NYHA class I, and enjoy a normal social lifestyle. The Ross procedure may be offered as a low-risk alternative in adolescents and young adults with a bicuspid aortic valve. Although the inclusion cylinder technique might help to prevent root dilatation, continued patient evaluation with regard to root sizing, evidence of neoaortic valve degeneration and homograft dysfunction is required in the long term.


Intraoperative Ultrasound for Extracting Deep-Seated Radio-Opaque Foreign Body from Calf: A Case Report.
A 50-year-old man presented with chronic refractory symptoms of radiating leg pain with muscle cramps because of a retained bullet in the calf after being shot in 1990. Radiographs confirmed the bullet lodged in posterolateral aspect of calf abutting proximal fibula. An intraoperative point-of-care ultrasound aided in accurate localization of bullet, thereby facilitating precise planning of surgical incision and subsequent removal. Ultrasound can be used as an alternative tool for safe surgical extraction of deep-seated metallic object with minimal tissue dissection, obviating the need for C-arm.


Short- and long-term outcomes of laparoscopic organ-sparing resection in pancreatic neuroendocrine tumors: a single-center experience.
Laparoscopic organ-sparing pancreatectomy (LOSP) is an ideal therapeutic option in selected cases of pancreatic neuroendocrine tumors (PNETs). Nevertheless, given the low frequency of PNETs, there is scarce evidence regarding short and particularly long-term outcomes of LOSP in this clinical setting. All patients with PNETs who underwent surgery (under a LOSP policy) were retrospectively reviewed from a prospective database maintained at our center. Preoperative characteristics, operative data, pathological features and postoperative outcomes were analyzed. Between December 2003 and December 2015, 36 patients with PNETs underwent laparoscopic resections. Ten were functional tumors, 26 non-functional and 16 were "incidental" cases. The following procedures were performed: one enucleation, eight central pancreatectomies (LCP), one resection of the uncinate process and 26 distal pancreatectomies (DP) (15 of them laparoscopic vessels-preserving). There were no conversions to open surgery, and no drains were routinely left. Mean operative time was 288 min (SD 99). Hospital stay was 6 days. Eighteen patients (50%) experienced some complication of which most were mild (Clavien-Dindo I/II). Three postoperative bleedings occurred: two grade B/one grade C; two required laparoscopic reoperation. Thirteen (36.1%) patients developed peripancreatic fluid collections: two were symptomatic and were managed with transgastric drainage (one presented post-puncture abscesification requiring surgical drainage and splenectomy). Four patients (11%)-one DP and three LCP-developed new-onset pancreatogenic diabetes mellitus (NODM) in the long term. According to the European Neuroendocrine Tumor Society, 19 cases were stage I, seven IIA, two IIIA, one IIIB and seven stage IV. Over a mean follow-up of 51 months, two patients died, one due to recurrence of the tumor and another due to cirrhosis. The existing different surgical options must be individually considered according to the location and particular characteristics of every tumor. Results from this single-center study document the effectiveness of LOSP in selected cases of PNETs.


Performance of the Personality Inventory for Youth validity scales.
Response sets as well as cognitive and academic deficits compromise the validity of child and adolescent self-report of emotional adjustment. Three studies using clinical and asymptomatic samples of 4th to 12th grade students detail applications of the four validity scales of the Personality Inventory for Youth (PIY), namely, (a) Validity (VAL) a scale of six highly improbable statements, (b) Inconsistency (INC) consisting of pairs of highly correlated statements, (c) Dissimulation (FB) constructed of statements that were infrequent and characteristic of intentional distortion, and (d) Defensiveness (DEF) an extension of the Lie scale of the parent-report Personality Inventory for Children. The effects of minimizing, malingering, and random response sets on the PIY validity scales are reported. The importance of such validity scales derived from child and adolescent response is discussed.


Patterns of shrub expansion in Alaskan arctic river corridors suggest phase transition.
Recent increases in deciduous shrub cover are a primary focus of terrestrial Arctic research. This study examined the historic spatial patterns of shrub expansion on the North Slope of Alaska to determine the potential for a phase transition from tundra to shrubland. We examined the historic variability of landscape-scale tall shrub expansion patterns on nine sites within river valleys in the Brooks Range and North Slope uplands (BRNS) between the 1950s and circa 2010 by calculating percent cover (PCTCOV), patch density (PADENS), patch size variability (CVSIZE), mean nearest neighbor distance (MEDIST) and the multi-scale information fractal dimension (d I ) to assess spatial homogeneity for shrub cover. We also devised conceptual models for trends in these metrics before, during, and after a phase transition, and compared these to our results. By developing a regression equation between PCTCOV and d I and using universal critical d I values, we derived the PCTCOV required for a phase transition to occur. All nine sites exhibited increases in PCTCOV. Five of the nine sites exhibited an increase in PADENS, seven exhibited an increase in CVSIZE, and five exhibited a decrease in MEDIST. The d I values for each site exceeded the requirements necessary for a phase transition. Although fine-scale heterogeneity is still present, landscape-scale patterns suggest our study areas are either currently in a state of phase transition from tundra to shrubland or are progressing towards spatial homogeneity for shrubland. Our results indicate that the shrub tundra in the river valleys of the north slope of Alaska has reached a tipping point. If climate trends observed in recent decades continue, the shrub tundra will continue towards homogeneity with regard to the cover of tall shrubs.


A study of the factors which influence the length of hospital stay of stroke patients.
To examine the factors which influence the length of hospitalization of stroke patients. Analysis of the relative importance of 10 preselected variables on the length of hospital stay of all patients admitted with a clinical diagnosis of stroke. The data were collected prospectively. Two teaching hospitals serving the city of Southampton and southwest Hampshire, England (approximate population 450000). Forty-six consecutive stroke patients. Data were complete on 38 patients. The mean and (median) length of hospital stay was 74.9 (80.5) days for men and 74.7 (73.5) for women. The mean age of women in the study sample was higher than that of men (73.2 vs 71.6). Patients who were less than 70 years of age stayed shorter periods in hospital than older subjects. Other factors associated with shorter hospitalization were a stroke type other than total anterior circulation infarct, a Barthel score of 12 or more on admission or at the time of discharge and a frequency of consultants' ward rounds of more than one per week. A delay in the provision of equipment and home adaptations and waiting for placement in a private nursing home were the best predictors of long hospital stays of stroke patients. Early liaison of rehabilitation staff with Social Services in order to secure the quick provision of environmental aids and adaptations or placement in residential care of stroke patients with a poor prognosis for functional recovery would probably reduce the unnecessary hospitalization of these patients.


The role of supplementary eye field in goal-directed behavior.
The medial frontal cortex has been suggested to play a role in the control, monitoring, and selection of behavior. The supplementary eye field (SEF) is a cortical area within medial frontal cortex that is involved in the regulation of eye movements. Neurophysiological studies in the SEF of macaque monkeys have systematically investigated the role of SEF in various behavioral control and monitoring functions. Inhibitory control studies indicate that SEF neurons do not directly participate in the initiation of eye movements. Instead, recent value-based decision making studies suggest that the SEF participates in the control of eye movements by representing the context-dependent action values of all currently possible oculomotor behaviors. These action value signals in SEF would be useful in directing the activity distribution in more primary oculomotor areas, to guide decisions towards behaviorally optimal choices. SEF also does not participate in the fast, inhibitory control of eye movements in response to sudden changes in the task requirements. Instead, it participates in the long-term regulation of oculomotor excitability to adjust the speed-accuracy tradeoff. The context-dependent control signals found in SEF (including the action value signals) have to be learned and continuously adjusted in response to changes in the environment. This is likely the function of the large number of different response monitoring and evaluation signals in SEF. In conclusion, the overall function of SEF in goal-directed behavior seems to be the learning of context-dependent rules that allow predicting the likely consequences of different eye movements. This map of action value signals could be used so that eye movements are selected that best fulfill the current long-term goal of the agent.


Pneumotoxicity associated with immune checkpoint inhibitor therapies.
Immune checkpoint inhibitor therapies represent a new paradigm in cancer therapeutics, in which the targets are not the cancer cells, but the body's own immune system. Harnessing the immune system to better fight cancer has generated a unique spectrum of immune-related adverse events (IrAEs) that effect virtually every major organ system. Although lung involvement is less common than other forms of IrAEs, its consequences are potentially lethal. This review focuses on the evolving spectrum of lung toxicities associated with the two major classes of immune checkpoint inhibitor therapies, cytotoxic T-cell ligand-4, and programed cell death-1 (PDL-1). Lung injury was not reported in the earliest clinical trials of immune checkpoint inhibitors. More recent studies, however, have described unique radiographic and clinical toxicity profiles that differ significantly from lung injury patterns associated with conventional cytotoxic therapies. The pathophysiologic mechanisms of immune-related lung injury, its radiographic and clinical disease spectrum, associated risk factors, and optimal treatment strategies remain poorly understood. Adverse immune-mediated lung events are increasingly recognized as unique and potentially life-threatening sequelae of checkpoint inhibitor therapies. Early recognition of symptoms and radiographic abnormalities is essential to proper management and successful outcome.


[Dreams in ancient Hebrew sources].
As in many cultures dreams are, in Hebrew sources, the object of numerous questions where are dreams from? Which is their function? Are they a physical or metaphysical phenomenon? The article analyzes the topic of nature of dreams in the Bible, with a particolar attention devoted to the Joseph's history. Talmudic text are, in particular, rich in references.


Efferent connections of the subfascicular area of the mesodiencephalic junction and its possible involvement in stimulation-produced analgesia.
Stimulation-produced analgesia (SPA) can be induced in animals and humans from an ill-defined area of the mesodiencephalic junction lying beneath the parafascicular complex of the medial thalamus. Neurons projecting to the spinal cord, the subnucleus caudalis of the trigeminal complex, the nuclei raphé magnus and dorsalis, the inferior olivary complex and the amygdala could be observed in this area, using the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. On the basis of the locations of the neurons projecting to these different areas, 3 subnuclei were delineated: the rostral interstitial nucleus of the MLF lying laterally along the medial tip of the medial lemniscus, containing a few neurons projecting to the raphé nuclei and the inferior olivary complex; the subparafascicular nucleus (spf) lying medially in the rostralmost part of the area and containing neurons projecting to the amygdala and basal ganglia; the subfascicular area of the mesodiencephalic junction lying medially and caudal to the spf and containing neurons projecting to the raphé nuclei, the inferior olive, the caudalis subnucleus of the trigeminal complex and the spinal cord. The possibility that the subfascicular area of the mesodiencephalic junction is the effective site for SPA is discussed.


Diagnostic thresholds for ambulatory blood pressure moving lower: a review based on a meta-analysis-clinical implications.
Upper limits of normal ambulatory blood pressure (ABP) have been a matter of debate in recent years. Current diagnostic thresholds for ABP rely mainly on statistical parameters derived from reference populations. Recent findings from the International Database of Ambulatory Blood Pressure in Relation to Cardiovascular Outcome (IDACO) provide outcome-driven thresholds for ABP. Rounded systolic/diastolic thresholds for optimal ABP were found to be 115/75 mm Hg for 24 hours, 120/80 mm Hg for daytime, and 100/65 mm Hg for nighttime. The corresponding rounded thresholds for normal ABP were 125/75 mm Hg, 130/85 mm Hg, and 110/70 mm Hg, respectively, and those for ambulatory hypertension were 130/80 mm Hg, 140/85 mm Hg, and 120/70 mm Hg. However, in clinical practice, any diagnostic threshold for blood pressure needs to be assessed in the context of the patient's overall risk profile. The IDACO database is therefore being updated with additional population cohorts to enable the construction of multifactorial risk score charts, which also include ABP.


MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography.
MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production. We previously observed that the TIR domain of MAL (MALTIR) forms filaments in vitro and induces formation of crystalline higher-order assemblies of the MyD88 TIR domain (MyD88TIR). These crystals are too small for conventional X-ray crystallography, but are ideally suited to structure determination by microcrystal electron diffraction (MicroED) and serial femtosecond crystallography (SFX). Here, we present MicroED and SFX structures of the MyD88TIR assembly, which reveal a two-stranded higher-order assembly arrangement of TIR domains analogous to that seen previously for MALTIR. We demonstrate via mutagenesis that the MyD88TIR assembly interfaces are critical for TLR4 signaling in vivo, and we show that MAL promotes unidirectional assembly of MyD88TIR. Collectively, our studies provide structural and mechanistic insight into TLR signal transduction and allow a direct comparison of the MicroED and SFX techniques.


Computational characterization of reflectance confocal microscopy features reveals potential for automated photoageing assessment.
Skin photoageing results from a combination of factors including ultraviolet (sun) exposure, leading to significant changes in skin morphology and composition. Conventional methods assessing the degree of photoageing, in particular histopathological assessment involve an invasive multistep process. Advances in microscopy have enabled a shift towards non-invasive in vivo microscopy techniques such as reflectance confocal microscopy (RCM) in this context. Computational image analysis of RCM images has the potential to be of use in the non-invasive assessment of photoageing. In this report, we computationally characterized a clinical RCM data set from younger and older Caucasians with varying levels of photoageing. We identified several mathematical relationships that related to the degree of photoageing as assessed by conventional scoring approaches (clinical photography, SCINEXA and RCM). Furthermore, by combining the mathematical features into a single computational assessment score, we observed significant correlations with conventional RCM (P < 0.0001) and the other clinical assessment techniques.


Molecular determinants and genetic modifiers of aggregation and toxicity for the ALS disease protein FUS/TLS.
TDP-43 and FUS are RNA-binding proteins that form cytoplasmic inclusions in some forms of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Moreover, mutations in TDP-43 and FUS are linked to ALS and FTLD. However, it is unknown whether TDP-43 and FUS aggregate and cause toxicity by similar mechanisms. Here, we exploit a yeast model and purified FUS to elucidate mechanisms of FUS aggregation and toxicity. Like TDP-43, FUS must aggregate in the cytoplasm and bind RNA to confer toxicity in yeast. These cytoplasmic FUS aggregates partition to stress granule compartments just as they do in ALS patients. Importantly, in isolation, FUS spontaneously forms pore-like oligomers and filamentous structures reminiscent of FUS inclusions in ALS patients. FUS aggregation and toxicity requires a prion-like domain, but unlike TDP-43, additional determinants within a RGG domain are critical for FUS aggregation and toxicity. In further distinction to TDP-43, ALS-linked FUS mutations do not promote aggregation. Finally, genome-wide screens uncovered stress granule assembly and RNA metabolism genes that modify FUS toxicity but not TDP-43 toxicity. Our findings suggest that TDP-43 and FUS, though similar RNA-binding proteins, aggregate and confer disease phenotypes via distinct mechanisms. These differences will likely have important therapeutic implications.


Genetic variants in Hippo pathway genes YAP1, TEAD1 and TEAD4 are associated with melanoma-specific survival.
Cutaneous melanoma (CM) is the most lethal form of skin cancers. The Hippo pathway controls cell migration, development and sizes of the organs in diverse species, and deregulation of this pathway may affect CM progression and prognosis. Therefore, we hypothesized that genetic variants of Hippo pathway genes might predict survival of CM patients. We used the genotyping data of 1,115 common single nucleotide polymorphisms (SNPs) in the 12 pathway core genes (i.e., MST1, MST2, SAV1, LATS1, LATS2, MOB1A, MOB1B, YAP1, TEAD1, TEAD2, TEAD3 and TEAD4) from the dataset of our previously published CM genome-wide association study and comprehensively analyzed their associations with CM-specific survival (CSS) in 858 CM patients by using the Kaplan-Meier analyses and Cox proportional hazards regression models. We found a predictive role of YAP1 rs11225163 CC, TEAD1 rs7944031 AG+GG and TEAD4 rs1990330 CA+AA in the prognosis of CM. In addition, patients with an increasing number of unfavorable genotypes (NUG) had a markedly increased risk of death. After incorporating NUG in the model with clinical variables, the new model showed a significantly improved discriminatory ability to classify CSS (AUC increased from 82.03% to 84.56%). Our findings suggest that genetic variants of Hippo pathway genes, particularly YAP1 rs11225163, TEAD1 rs7944031 and TEAD4 rs1990330, may independently or jointly modulate survival of CM patients. Additional large, prospective studies are needed to validate these findings.


Conceptual size representation in ventral visual cortex.
Recent findings suggest that visual objects may be mapped along the ventral occipitotemporal cortex according to their real-world size (Konkle and Oliva, 2012). It has been argued that such mapping does not reflect an abstract, conceptual size representation, but rather the visual or functional properties associated with small versus big real-world objects. To determine whether a more abstract conceptual size representation may affect visual cortical activation we used meaningless geometrical shapes, devoid of semantic or functional associations, which were associated with specific size representations by virtue of extensive training. Following training, participants underwent functional magnetic resonance imaging (fMRI) scanning while performing a conceptual size comparison task on the geometrical shapes. In addition, a size comparison task was conducted for numeral digits denoting small and big numbers. A region-of-interest analysis revealed larger blood oxygenation level dependent (BOLD) responses for conceptually 'big' than for conceptually 'small' shapes, as well as for big versus small numbers, within medial (parahippocampal place area, PPA) and lateral (occipital place area, OPA) place-selective regions. Processing of the 'big' visual shapes further elicited enhanced activation in early visual cortex, possibly reflecting top-down projections from PPA. By using arbitrary shapes and numbers we minimized visual, categorical, or functional influences on fMRI measurement, providing evidence for a possible neural mechanism underlying the representation of abstract conceptual size within the ventral visual stream.


The complexity of eye-hand coordination: a perspective on cortico-cerebellar cooperation.
Eye-hand coordination (EHC) is a sophisticated act that requires interconnected processes governing synchronization of ocular and manual motor systems. Precise, timely and skillful movements such as reaching for and grasping small objects depend on the acquisition of high-quality visual information about the environment and simultaneous eye and hand control. Multiple areas in the brainstem and cerebellum, as well as some frontal and parietal structures, have critical roles in the control of eye movements and their coordination with the head. Although both cortex and cerebellum contribute critical elements to normal eye-hand function, differences in these contributions suggest that there may be separable deficits following injury. As a preliminary assessment for this perspective, we compared eye and hand-movement control in a patient with cortical stroke relative to a patient with cerebellar stroke. We found the onset of eye and hand movements to be temporally decoupled, with significant decoupling variance in the patient with cerebellar stroke. In contrast, the patient with cortical stroke displayed increased hand spatial errors and less significant temporal decoupling variance. Increased decoupling variance in the patient with cerebellar stroke was primarily due to unstable timing of rapid eye movements, saccades. These findings highlight a perspective in which facets of eye-hand dyscoordination are dependent on lesion location and may or may not cooperate to varying degrees. Broadly speaking, the results corroborate the general notion that the cerebellum is instrumental to the process of temporal prediction for eye and hand movements, while the cortex is instrumental to the process of spatial prediction, both of which are critical aspects of functional movement control.


Apoptosis of human lung cancer cells by curcumin mediated through up-regulation of "growth arrest and DNA damage inducible genes 45 and 153".
The expression of "growth arrest and DNA damage inducible genes 45 and 153" is related to apoptotic induction of cells. GADD45 is an effector gene of the tumor suppressor p53, and GADD153 is associated with cellular function of cancer prevention. Curcumin, isolated from the plant Curcuma longa (LINN), has been investigated as a promising cancer preventive in food because curcumin, a phenolic and coloring compound, is widely ingested in the Indian subcontinent. However, the exact mechanisms of action of curcumin have not yet been clearly elucidated. Based on our successful results with green tea catechins as cancer preventive, we studied the relationship between the expression of GADD45 and 153 and apoptotic induction in human lung cancer cell line PC-9. In our study curcumin increased the expression of GADD45 and 153 in a p53-independent manner. Curcumin also inhibited the growth of PC-9 cells and induced G(1)/S arrest of the cell-cycle followed by strong induction of apoptosis. Treatment with GADD45 and 153 small interfering RNAs (siRNAs) inhibited the apoptotic induction in PC-9 cells by curcumin. Moreover, curcumin induced the expression of cyclin dependent kinase inhibitor genes p21 and p27, while it inhibited the expression of numerous genes, including Bcl-2, cyclin D1, CDK2, CDK4 and CDK6. All the results with PC-9 cells suggest that the up-regulation of GADD45 and 153 by curcumin is a prime mechanism in the anticancer activity of curcumin.


Epidermal growth factor receptor (EGFR) polymorphisms and breast cancer among Hispanic and non-Hispanic white women: the Breast Cancer Health Disparities Study.
The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases, functions in cellular processes essential to the development of cancer. Overexpression of EGFR in primary breast tumors has been linked with poor prognosis. We investigated the associations between 34 EGFR tagging SNPs and breast cancer risk and breast cancer-specific mortality in 4,703 Hispanic and 3,030 non-Hispanic white women from the Breast Cancer Health Disparities Study. We evaluated associations with risk of breast cancer defined by estrogen/progesterone receptor (ER/PR) tumor phenotype. Only one association remained statistically significant after adjusting for multiple comparisons. Rs2075112GA/AA was associated with reduced risk for ER-/PR+ tumor phenotype (odds ratio (OR), 0.34; 95% confidence interval (CI) 0.18-0.63, p adj=0.01). All additional results were significant prior to adjustment for multiple comparisons. Two of the EGFR polymorphisms were associated with breast cancer risk in the overall study population (rs11770531TT: OR, 0.56, 95% CI 0.37-0.84; and rs2293348AA: OR, 1.20, 95% CI 1.04-1.38) and two polymorphisms were associated with risk among Hispanics: rs6954351AA: OR, 2.50, 95% CI 1.32-4.76; and rs845558GA/AA: OR, 1.15, 95% CI 1.01-1.30. With regard to breast cancer-specific mortality, we found positive associations with rs6978771TT hazard ratio (HR), 1.68; 95% CI 1.11-2.56; rs9642391CC HR, 1.64; 95% CI 1.04-2.58; rs4947979AG/GG HR, 1.36; 95% CI 1.03-1.79; and rs845552GG HR, 1.62; 95% CI 1.05-2.49. Our findings provide additional insight for the role of EGFR in breast cancer development and prognosis. Further research is needed to elucidate EGFR's contribution to ethnic disparities in breast cancer.


Clinical Course of 195 Critically Ill COVID-19 Patients: A Retrospective Multicenter Study.
Coronavirus disease-2019 (COVID-19) outbreak has spread around the world. However, the dynamic course of critically ill COVID-19 has not been described thoroughly. We retrospectively analyzed 195 critically ill COVID-19 patients in Hubei province, China, between January 5, 2020 and April 3, 2020. Epidemiologic data, clinical features, treatments, and outcomes were collected and analyzed. Most critically ill patients were older with higher Acute Physiology and Chronic Health Evaluation II scores. After critical illness onset, a total of 181 (92.8%) patients received ventilation support, of which 84 (43.1%) received noninvasive and 97 (49.7%) received invasive mechanic ventilation (IMV). Among the 97 patients with IMV, 28 (28.9%) received prone ventilation, 57 (58.8%) received neuromuscular blocked therapy, and 22 (11.3%) received tracheostomy due to prolonged ventilator use. Early hypoxemia, subsequent hypercapnia, pulmonary hypertension, and finally pulmonary fibrosis were notable in the clinical course of acute respiratory distress syndrome (ARDS). Eighty-nine (45.6%) patients presented with shock. Acute kidney injury (29.7%) and secondary infection (28.2%) were also notable. The overall mortality of critically ill patients at day 28 was 42.1%. Intensive care unit (ICU) mortality was around 33%, as 16 patients died prior to ICU admission. A low PaO2/FiO2 ratio was an independent risk factor for death. High viral load was observed in most non-survivors. ARDS and shock were notable in the critical illness of COVID-19. Ventilation support and hemodynamic support were the cornerstones for critical care. High viral load was associated with death of critically ill COVID-19 patients.


Prevalence and Attitudes Regarding Marijuana Use Among Adolescents Over the Past Decade.
Adolescent marijuana prevalence has not increased since 2005 despite a substantial decrease in the percentage of adolescents who believe marijuana use leads to great risk of harm. This finding calls into question the long-standing, inverse connection between marijuana prevalence and perceived risk of use, a connection central to many arguments opposing marijuana legalization. We tested 2 hypotheses for why marijuana prevalence did not increase after 2005: (1) decreases in adolescent use of cigarettes and alcohol reduced risk for marijuana use and counteracted the expected risk in marijuana prevalence, and/or (2) perceived risk of harm now plays a smaller role in marijuana use. Data came from the annual, nationally-representative Monitoring the Future study from 1991 to 2016, in which 1 100 000 US students in eighth, 10th, and 12th grade were surveyed. The entire sample was stratified into 3 mutually exclusive and exhaustive groups on the basis of cigarette and alcohol use. Within each of the 3 groups, marijuana prevalence increased from 2005 to 2016. Paradoxically, when the 3 groups were combined into 1 analysis pool, overall marijuana prevalence did not increase. The seeming paradox results from a decline in the percentage of adolescents who used cigarettes; as this group grew smaller, so too did its disproportionately large contribution to overall marijuana prevalence. Perceived risk of harm from marijuana remained a strong indicator of use throughout 2005 to 2016. Perceived risk of marijuana remains tightly associated with use, and adolescent marijuana prevalence today would be at or near record highs if cigarette use had not declined since 2005, according to study projections.


The Effect of National Pneumococcal Vaccination Program on Incidence of Postmeningitis Sensorineural Hearing Loss and Current Treatment Modalities.
The aim of the present study was to investigate the effect of the national pneumococcal vaccination program on postmeningitis sensorineural hearing loss (SNHL). Overall, 2751 patients (2615 cochlear implantation and 136 auditory brainstem implantation) who underwent cochlear implantation (CI) and auditory brainstem implantation (ABI) at a tertiary referral hospital otolaryngology clinic were retrospectively analyzed. One hundred sixteen patients with a history of meningitis were included in the study. Patients were evaluated for their age at the time of surgery, gender, computerized tomography (CT) and magnetic resonance imaging (MRI) findings, implant type, side, and incidence before and after the vaccination program. When patients with cochlear implants or ABI were examined, the incidence of meningitis-induced hearing loss was 6.2% in the pre-vaccination period and 0.6% in the post-vaccination period. There is a significant difference between them when compared by chi-square test (p<0.001). The most important finding of the present study is the dramatic decrease in the number of CI and ABI surgeries performed in patients with SNHL due to meningitis. This shows the effectivity of pneumococcal vaccination in this special group of patients. If total ossification is detected on CT of patients with postmeningitis, ABI should be preferred to CI.


Should oncologists trust cannabinoids?
Cannabis enjoyed a "golden age" as a medicinal product in the late 19th, early 20th century, but the increased risk of overdose and abuse led to its criminalization. However, the 21st century have witnessed a resurgence of interest and a large body of literature regarding the benefits of cannabinoids have emerged. As legalization and decriminalization have spread around the world, cancer patients are increasingly interested in the potential utility of cannabinoids. Although eager to discuss cannabis use with their oncologist, patients often find them to be reluctant, mainly because clinicians are still not convinced by the existing evidence-based data to guide their treatment plans. Physicians should prescribe cannabis only if a careful explanation can be provided and follow up response evaluation ensured, making it mandatory for them to be up to date with the positive and also negative aspects of the cannabis in the case of cancer patients. Consequently, this article aims to bring some clarifications to clinicians regarding the sometimes-confusing various nomenclature under which this plant is mentioned, current legislation and the existing evidence (both preclinical and clinical) for the utility of cannabinoids in cancer patients, for either palliation of the associated symptoms or even the potential antitumor effects that cannabinoids may have.


The 5-methylcytosine content of DNA from human tumors.
The over-all 5-methylcytosine (m5C) content of DNA from normal tissues varies considerably in a tissue-specific manner. By high-performance liquid chromatography, we have examined the m5C contents of enzymatic digests of DNA from 103 human tumors including benign, primary malignant and secondary malignant neoplasms. The diversity and large number of these tumor samples allowed us to compare the range of DNA methylation levels from neoplastic tissues to that of normal tissues from humans. Most of the metastatic neoplasms had significantly lower genomic m5C contents than did most of the benign neoplasms or normal tissues. The percentage of primary malignancies with hypomethylated DNA was intermediate between those of metastases and benign neoplasms. These findings might reflect an involvement of extensive demethylation of DNA in tumor progression. Such demethylation could be a source of the continually generated cellular diversity associated with cancer.


Long-term changes in childhood malnutrition are associated with long-term changes in maternal BMI: evidence from Bangladesh, 1996-2011.
Nutritional transition (from under- to overnutrition) among women of reproductive age (15-49 y) is becoming increasingly common in many developing countries, including Bangladesh. However, the influence of this transition on the nutritional status of children <5 y of age (U5s) is unknown. The aim was to determine whether a nutritional transition has taken place in the past 15 y (1996-2011) among U5s and their mothers in Bangladesh and to examine how the association between maternal body mass index (BMI) and malnutrition in U5s has changed over time. We analyzed data assembled from 5 Demographic and Health Surveys conducted between 1996 and 2011 in Bangladesh to describe the nutritional status of 28,941 U5s and their mothers. A Poisson regression model was used to examine the associations between maternal BMI and stunting, underweight, and wasting in U5s over time. A nutritional transition among mothers of U5s was observed between 1996 and 2011. The height- or length-for-age and weight-for-age z score distributions of U5s showed consistent improvement; however, there was no indication of a nutritional transition. An interaction was found between maternal BMI categorized as underweight [BMI (kg/m2) <18.5], healthy BMI (BMI: 18.5-24.9), and overweight or obese (BMI ≥25) and year of survey on the risks of stunting and underweight in children. In 1996, children of underweight mothers had a 5% higher risk of being stunted than those born to healthy-BMI mothers (RR: 1.05; 95% CI: 1.00, 1.10); in 2011, children of underweight mothers had a 21% higher risk of being stunted (RR: 1.21; 95% CI: 1.13, 1.30). Maternal overweight or obesity was associated with a reduced risk of malnutrition in children. A nutritional transition among U5s has yet to occur in Bangladesh. However, our results indicate that improvement in maternal BMI in the past 15 y was accompanied by a reduction in malnutrition in U5s.


[2 stages in the formation of the humoral component of immunological reactivity in acantholytic pemphigus].
A study was made of the time course of the blood serum and plasma levels of large-, medium-, and small-sized CIC in patients with acantholytic pemphigus (n = 15) and healthy donors (n = 15). We could find no comparative data in the literature on blood serum and plasma CICs in acantholytic pemphigus (AP). Blood to be assayed was taken from those AP patients receiving course treatments by generally recognized techniques during AP progression, stabilization, and significant regression of the eruption. In the normal state as well as during progression and stabilization of the dermatosis manifestations large and medium CICs in plasma exceeded those in serum 1.3-2.2-fold. On the contrary, in plasma the above values got lower during the regression stage of the eruption (table). The findings available allow us to assume that there are two distinct stages in the process of formation of the humoral component of immunologic reactivity in AP.


Obesity associated molecular forms of C-reactive protein in human.
To describe novel C-reactive protein (CRP) molecular forms (mf) in human plasma. Five novel CRP-mfs, disctinct from the previously described native (nCRP) and modified (mCRP) C-reactive proteins, were separated from human plasma by polyacrylamide gel electrophoresis and immunodetected by western blot in subjects with or without increased BMI, cardiovascular disease (CVD), and diabetes (n = 1800). Three of the five CRP-mfs were present in all samples. One, CRPmf-4, was present in a subgroup of subjects and its presence was associated with elevated body mass index (BMI). CRP-mf-5 was present in about 2% of the subjects and was not associated with any other parameters. The presence or distribution of the 5 CRP-mfs were not Ca2+-dependent. Crossed immuno-localization experiments indicated that none of the CRP-mfs were complexed with any of the lipoprotein classes or with signature proteins of the complement-factor. Moreover, the distribution of CRP-mfs were not significantly correlated with plasma CRP levels. CRP-mf-4 was significantly associated with increased BMI, but not with other parameters of the metabolic syndrome (HDL-C and triglyceride levels, and diabetes). We have identified five new CRP-mfs out of which CRP-mf-4 was significantly associated with obesity. We have shown that oligomerization of CRP was not calcium dependent. We hypothesize that adipose tissue produces a factor which influences the formation of CRP mf-4. CRP-mfs might be used as an obesity-associated inflammatory marker.


Voices behind the left shoulder: two patients with right-sided temporal lobe epilepsy.
Auditory vocal hallucinations are sometimes observed in temporal-lobe epilepsy, but are a frequent sign of psychosis and may rarely be mistaken for the latter. Here we report two patients who suffered from auditory vocal hallucinations, described as unintelligible human voices perceived at their left side during epileptic seizures. MEG revealed interictal epileptic discharges within the anterior partition of the right superior temporal gyrus; signal-to-noise ratio of these discharges was overall poor in EEG. The findings suggest that auditory vocal hallucinations without verbal content can evolve in the right hemisphere and are probably independent of language lateralization. This is in accordance with evidence from functional imaging, whereas most previous reports of seizures with auditory vocal hallucinations were confined to the left hemisphere.


Index cluster study of dengue virus infection in Nicaragua.
Traditional study designs do not identify acute asymptomatic or pre-symptomatic dengue virus (DENV) infections, thus limiting our understanding of immunologic and viral factors that modulate infection outcome. In the 2006 and 2007 dengue seasons, we conducted a pilot index cluster study in Managua, Nicaragua, in which 442 persons living within 50 meters of 22 index cases identified through an ongoing pediatric cohort study were evaluated for DENV infection. Post-enrollment and pre-enrollment DENV infections were confirmed in 12 (2.7%) and 19 (4.3%) contacts, respectively. Five (42%) post-enrollment infections were asymptomatic, and DENV-2 was identified in 9 (75%) infections. Phylogenetic analysis with full-length DENV genomic sequence from contacts, index cases, and cohort dengue cases indicated focal transmission and infection outside the local area. We demonstrate the feasibility of identification of acute asymptomatic and pre-symptomatic cases in urban Latin America, the first report of such a study in the Americas, and identify age and concomitant immunity to DENV of contacts as a key factor in index cluster study design.


AM noise impact on low level phase noise measurements.
The influence of the source AM noise in microwave residual phase noise experiments is investigated. The noise floor degradation problem, caused by the parasitic detection of this type of noise by an unperfectly balanced mixer, is solved thanks to a refinement of the quadrature condition. The parasitic noise contribution attributable to the AM to PM (phase modulation) conversion occurring in the device under test is minimized through the development of a dedicated microwave source featuring an AM noise level as low as -170 dBc/Hz at 10 kHz offset from a 3.5 GHz carrier.


Iron-oxidizing bacteria: an environmental and genomic perspective.
In the 1830s, iron bacteria were among the first groups of microbes to be recognized for carrying out a fundamental geological process, namely the oxidation of iron. Due to lingering questions about their metabolism, coupled with difficulties in culturing important community members, studies of Fe-oxidizing bacteria (FeOB) have lagged behind those of other important microbial lithotrophic metabolisms. Recently, research on lithotrophic, oxygen-dependent FeOB that grow at circumneutral pH has accelerated. This work is driven by several factors including the recognition by both microbiologists and geoscientists of the role FeOB play in the biogeochemistry of iron and other elements. The isolation of new strains of obligate FeOB allowed a better understanding of their physiology and phylogeny and the realization that FeOB are abundant at certain deep-sea hydrothermal vents. These ancient microorganisms offer new opportunities to learn about fundamental biological processes that can be of practical importance.


On-going clinical trials for elderly patients with a hematological malignancy: are we addressing the right end points?
Cancer societies and research cooperative groups worldwide have urged for the development of cancer trials that will address those outcome measures that are most relevant to older patients. We set out to determine the characteristics and study objectives of current clinical trials in hematological patients. The United States National Institutes of Health clinical trial registry was searched on 1 July 2013, for currently recruiting phase I, II or III clinical trials in hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. In the 1207 clinical trials included in this overview, patient-centered outcome measures such as quality of life, health care utilization and functional capacity were only incorporated in a small number of trials (8%, 4% and 0.7% of trials, respectively). Even in trials developed exclusively for older patients, the primary focus lies on standard end points such as toxicity, efficacy and survival, while patient-centered outcome measures are included in less than one-fifth of studies. Currently on-going clinical trials in hematological malignancies are unlikely to significantly improve our knowledge of the optimal treatment of older patients as those outcome measures that are of primary importance to this patient population are still included in only a minority of studies. As a scientific community, we cannot continue to simply acknowledge this issue, but must all participate in taking the necessary steps to enable the delivery of evidence-based, tailor-made and patient-focused cancer care to our rapidly growing elderly patient population.


Effects of rare earth element samarium doped zinc oxide nanoparticles on Mytilus galloprovincialis (Lamarck, 1819): Filtration rates and histopathology.
Doping was reported to improve the photo catalytic performance, antioxidant, antibacterial and other biological properties of nanoparticles. While, improving the nanoparticle properties, doping could change toxicity profile to living organism. Hence, the aim of this work was to assess the effects of samarium doped zinc oxide nanoparticles (Sm doped ZnO NPs) on the edible mussel Mytilus galloprovincialis. Sm doped ZnO nanoparticles were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) techniques. 156 mussels were exposed during 7 days to a low, intermediate and high concentration of Sm doped ZnO NPs (0.5, 1 and 1.5 mg/L, respectively). The filtration rates were assessed after 1 and 2 h. Histopathological alterations were determined in gills, digestive glands and gonads using a quantitative analysis. The filtration rates decreased in all individuals exposed to Sm doped ZnO NPs, a significant decrease was noted with the low and intermediate concentration (0.5 and 1 mg/L) of Sm doped ZnO NPs after 1 and 2 h, respectively. The histopathological index (Ih) estimated for gills, digestive glands and gonads showed differences depending on the organ and the nanoparticle concentration. The highest Ih were reported for digestive glands and female gonads exposed to the intermediate concentration (1 mg/L) of Sm doped ZnO NPs. As for gills and male gonads, the highest Ih were noted with the high concentration (1.5 mg/L) of Sm doped ZnO NPs. Results from this study revealed the toxicity of Sm doped ZnO NPs in Mytilus galloprovincialis gills, digestive glands and gonads. The toxicity induced by this nanoparticle varies depending on the organ and the concentration.


Community utilization of risk and protective factor data for prevention planning in Chile and Colombia.
Many effective community health service delivery systems implemented in the USA assess risk and protective factors (RPFs) for youth problem behaviors in a community, and report these data back to local coalitions for prevention planning. This study examined whether community prevention coalitions in Chile and Colombia perceived these reports of RPFs-based on the results of the Communities That Care Youth Survey-to be understandable, valid, useful, and worth disseminating. Thematic content analysis was used to analyze qualitative data collected from 7 focus groups with 75 coalition members. Results indicated heterogeneity between and within coalitions in terms of participants' understanding of RPFs. However, most participants found reports of RPFs to be easy to understand, thorough, 'true' to their communities, and useful for diagnosing and prioritizing needs, action planning, and mobilizing others in their communities. Findings suggest the viability of preventive systems that rely on community-level RPF data, for use in Latin America.


Codon 249 mutation in exon 7 of p53 gene in plasma DNA: maybe a new early diagnostic marker of hepatocellular carcinoma in Qidong risk area, China.
One of the characteristics of hepatocellular carcinoma (HCC) in Qidong area is the selective mutation resulting in a serine substitution at codon 249 of the p53 gene (1, 20), and it has been identified as a "hotspot" mutation in heptocellular carcinomas occurring in populations exposed to aflatoxin and with high prevalence of hepatitis B virus carriers (2,3,9, 10,16,24). We evaluated in this paper whether this "hotspot" mutation could be detected in cell-free DNA circulating in plasma of patients with hepatocellular carcinoma and cirrhosis in Qidong, China, and tried to illustrate the significance of the detection of this molecular biomarker. We collected blood samples from 25 hepatocellular carcinoma patients, 20 cirrhotic patients and 30 healthy controls in Qidong area. DNA was extracted and purified from 200 microl of plasma from each sample. The 249(Ser) p53 mutation was detected by restriction digestion analysis and direct sequencing of exon-7 PCR products. We found in exon 7 of p53 gene G-T transversion at the third base of codon 249 resulting 249(Arg) - 249(Ser) mutation in 10/25 (40 %) hepatocellular carcinoma cases, 4/20 (20 %) cirrhotics, and 2/30 (7 %) healthy controls. The adjusted odds ratio for having the mutation was 22.1(95 % CI, 3.2-91.7) for HCC cases compared to controls. These data show that the 249(Ser) p53 mutation in plasma is strongly associated with hepatocellular carcinoma in Qidong patients. We found this mutation was also detected, although it was at a much lower frequency, in plasma DNA of Qidong cirrhotics and healthy controls; We consider that these findings, together with the usual method of HCC diagnosis, will give more information in early diagnosis of HCC, and 249(Ser) p53 mutation should be developed to a new early diagnostic marker for HCC.


Improvement of tumor cell detection using a pool of monoclonal antibodies.
It has been proven that monoclonal antibodies which are not strictly tumor specific may be useful in clinical oncology for diagnosis and in in vitro therapy. These applications, however, are hampered by the heterogeneous expression on tumor cells of the epitopes defined by the majority of monoclonal antibodies produced so far. The use of combined monoclonals could complement their antitumor specificity and solve the problem. In this perspective we selected nine monoclonal antibodies directed against different antigens of primary and metastatic breast cancer cells. The reactivity of the pool of these nine monoclonals versus a single antibody (MBr1) was determined by immunofluorescence on tumor cell lines, on frozen sections of various carcinomas, and on live cells obtained from malignant effusions. The results obtained with the pool, compared to those using MBr1 alone, showed a remarkable increase in the number of immunopositive breast and other carcinomas and the number of immunopositive cells within each positive tumor. In fact, the percentage of immunoreactive breast carcinomas increased from 79% to 100%, and the percentage of immunoreactive carcinomas of other sites from 61% to 89%. In addition, the number of positive breast carcinomas showing 100% immunoreactive cells increased from 5% with MBr1 to 71% when the pool was used.


Matrix density drives 3D organotypic lymphatic vessel activation in a microfluidic model of the breast tumor microenvironment.
Lymphatic vessels (LVs) have been suggested as a preferential conduit for metastatic progression in breast cancer, where a correlation between the occurrence of lymph node metastasis and an increased extracellular matrix (ECM) density has been reported. However, the effect of ECM density on LV function is largely unknown. To better understand these effects, we used a microfluidic device to recreate tubular LVs in a collagen type I matrix. The density of the matrix was tailored to mimic normal breast tissue using a low-density collagen (LD-3 mg mL-1) and cancerous breast tissue using a high-density collagen (HD-6 mg mL-1). We investigated the effect of ECM density on LV morphology, growth, cytokine secretion, and barrier function. LVs cultured in HD matrices showed morphological changes as compared to LVs cultured in a LD matrix. Specifically, LVs cultured in HD matrices had a 3-fold higher secretion of the pro-inflammatory cytokine, IL-6, and a leakier phenotype, suggesting LVs acquired characteristics of activated vessels. Interestingly, LV leakiness was mitigated by blocking the IL-6 receptor on the lymphatic ECs, maintaining endothelium permeability at similar levels of LV cultured in a LD matrix. To recreate a more in vivo microenvironment, we incorporated metastatic breast cancer cells (MDA-MB-231) into the LD and HD matrices. For HD matrices, co-culture with MDA-MB-231 cells exacerbated vessel leakiness and secretion of IL-6. In summary, our data suggest that (1) ECM density is an important microenvironmental cue that affects LV function in the breast tumor microenvironment (TME), (2) dense matrices condition LVs towards an activated phenotype and (3) blockade of IL-6 signaling may be a potential therapeutic target to mitigate LV dysfunction. Overall, modeling LVs and their interactions with the TME can help identify novel therapeutic targets and, in turn, advance therapeutic discovery.


Genomic and proteomic approaches in comparative biochemistry and physiology.
Emerging technologies in genomics (e.g., cDNA library screening, DNA arrays), proteomics (e.g., two-dimensional gel electrophoresis and mass-spectroscopy fingerprinting), and metabolic regulation (e.g., elucidating protein-protein binding associations or signal transduction pathways) offer powerful tools for comparative biochemistry that will greatly increase our understanding of how animals adapt to environmental stress. The power of these new technologies and their potential application for physiological and ecophysiological research are illustrated with examples of recent advances in key fields. These include hypoxia/anoxia-responsive gene expression, the actions and regulation of the hypoxia-inducible transcription factor, the central role of the AMP-dependent kinase in mediating cellular responses to changing energy status, mammalian target of rapamycin mediation of nutrient signals in the control of protein synthesis and growth, proteomics approaches to identifying the physiological substrates of protein kinases, and the interactions of biochemistry and physiology in determining a net organismal response to high hematocrit values stimulated by erythropoietin. In particular, gene- and protein-screening technologies will drive a fundamental shift in the way that environmental stress effects on metabolism are evaluated by providing a holistic overview of the responses of a huge range of cell functions to stress and allowing researchers to identify multiple new areas of metabolic response that contribute to biochemical and physiological adaptation.


[Surgery of duodenal ulcer. In decline?].
The authors report their experience of the surgical treatment of duodenal ulcer disease and its complications over a 10 year period (1976-1986), i.e. 336 cases from a group of 10748 digestive tract endoscopies performed and 1126 duodenal ulcers identified (10.4%). The efficacy of new types of medical treatment (anti-secretory drugs, endoscopic hemostasis techniques, prostaglandins) and the improved follow-up of patients tend, despite the value and proven safety of Parietal-cell Vagotomy (elective procedure in 76% of the group), to modify: the epidemiological aspect of the disease in the sense of a decrease in the rate of ulcers with complications related to stenosis and perforation; the therapeutic aspect with more limited surgical indications. Is this the end of surgery for duodenal ulcer and its complications?


Structure and Elasticity of Mitochondrial Membranes: A Molecular Dynamics Simulation Study.
Mitochondria are known as the powerhouse of the cell because they produce energy in the form of adenosine triphosphate. They also have other crucial functions such as regulating apoptosis, calcium homeostasis, and reactive oxygen species production. To perform these diverse functions, mitochondria adopt specific structures and frequently undergo dynamic shape changes, indicating that their mechanical properties play an essential role in their functions. To gain a detailed understanding at the molecular level of the structure and mechanical properties of mitochondria, we carry out atomistic molecular dynamics simulations for three inner mitochondrial membranes and three outer mitochondrial membrane models. These models take into account variations in cardiolipin and cholesterol concentrations as well as the symmetry/asymmetry between the two leaflets. Our simulations allow us to calculate various structural quantities and the bending, twisting, and tilting elastic moduli of the membrane models. Our results indicate that the structures of the inner and outer mitochondrial membranes are quite similar and do not depend much on the variation in lipid compositions. However, the bending modulus of the membranes increases with increasing concentrations of cardiolipin or cholesterol but decreases with a membrane asymmetry. Notably, we found that the dipole potential of the membrane increases with an increasing cardiolipin concentration. Finally, possible roles of cardiolipin in regulating ion and proton currents and maintaining the cristate are discussed in some details.


Negative predictive value of intravenous contrast-enhanced CT of the abdomen for patients presenting to the emergency department with undifferentiated upper abdominal pain.
The purpose of this study is to calculate the negative predictive value (NPV) CT of the abdomen in patients presenting to the emergency department (ED) with undifferentiated upper abdominal pain. Approved by the hospital research ethics board, this retrospective study examined consecutive patients presenting to the ED with undifferentiated upper abdominal pain whose intravenous contrast-enhanced CT of the abdomen was reported as "normal" from June 2006-August 2010. Exclusion criteria included active malignancy, trauma, and known inflammatory bowel disease. True-negative (TN) vs. false-negative (FN) cases were categorized by consensus opinion of radiologist and emergency physician using a composite reference standard including clinical, laboratory, imaging, surgery, pathology, and patient self-reporting via phone questionnaire. The NPV was calculated with confidence intervals of 95%. The TN and FN groups were compared based on gender, age, site of pain, oral contrast use, and laboratory values. One hundred twenty-seven patients were included for analysis. The NPV was 64% (95% CI 55-72). The FN group had a higher proportion of patients with epigastric pain (p = 0.02) and a lower proportion of patients with left upper quadrant pain (p = 0.02). The WBC, lipase, and ALT were all higher in the FN group compared with the TN group. The most commonly missed pathologies were inflammatory conditions of the biliary tract and upper gastrointestinal systems. The NPV of CT for evaluation of undifferentiated upper abdominal pain in the ED was low at 64%. Physicians should consider this limitation and the commonly missed pathology when discharging patients with a "normal" CT report.


Population Genetics and Molecular Evolution of DNA Sequences in Transposable Elements. II. Accumulation of Variation and Evolution of a New Subfamily.
In order to understand how DNA sequences of transposable elements (TEs) evolve, extensive simulations were carried out. We first used our previous model, in which the copy number of TEs is mainly controlled by selection against ectopic recombination. It was found that along a simulation run, the shape of phylogeny changes quite much, from monophyletic trees to dimorphic trees with two clusters. Our results demonstrated that the change of the phase is usually slow from a monomorphic phase to a dimorphic phase, accompanied with a growth of an internal branch by accumulation of variation between two types. Then, the phase immediately changes back to a monomorphic phase when one group gets extinct. Under this condition, monomorphic and dimorphic phases arise repeatedly, and it is very difficult to maintain two or more different types of TEs for a long time. Then, how a new subfamily can evolve? To solve this, we developed a new model, in which ectopic recombination is restricted between two types under some condition, for example, accumulation of mutations between them. Under this model, because selection works on the copy number of each types separately, two types can be maintained for a long time. As expected, our simulations demonstrated that a new type arises and persists quite stably, and that it will be recognized as a new subfamily followed by further accumulation of mutations. It is indicated that how ectopic recombination is regulated in a genome is an important factor for the evolution of a new subfamily.


Cyclic pentapeptide cRGDfK enhances the inhibitory effect of sunitinib on TGF-β1-induced epithelial-to-mesenchymal transition in human non-small cell lung cancer cells.
In human lung cancer progression, the EMT process is characterized by the transformation of cancer cells into invasive forms that migrate to other organs. Targeting to EMT-related molecules is emerging as a novel therapeutic approach for the prevention of lung cancer cell migration and invasion. Traf2- and Nck-interacting kinase (TNIK) has recently been considered as an anti-proliferative target molecule to regulate the Wnt signaling pathway in several types of cancer cells. In the present study, we evaluated the inhibitory effect of a tyrosine kinase inhibitor sunitinib and the integrin-αⅤβ3 targeted cyclic peptide (cRGDfK) on EMT in human lung cancer cells. Sunitinib strongly inhibited the TGF-β1-activated EMT through suppression of Wnt signaling, Smad and non-Smad signaling pathways. In addition, the cRGDfK also inhibited the expression of TGFβ1-induced mesenchymal marker genes and proteins. The anti-EMT effect of sunitinib was enhanced when cRGDfK was treated together. When sunitinib was treated with cRGDfK, the mRNA and protein expression levels of mesenchymal markers were decreased compared to the treatment with sunitinib alone. Co-treatment of cRGDfK has shown the potential to improve the efficacy of anticancer agents in combination with therapeutic agents that may be toxic at high concentrations. These results provide new and improved therapies for treating and preventing EMT-related disorders, such as lung fibrosis and cancer metastasis, and relapse.


The nitric oxide (NO)-sensing repressor NsrR of Neisseria meningitidis has a compact regulon of genes involved in NO synthesis and detoxification.
We have analyzed the extent of regulation by the nitric oxide (NO)-sensitive repressor NsrR from Neisseria meningitidis MC58, using microarray analysis. Target genes that appeared to be regulated by NsrR, based on a comparison between an nsrR mutant and a wild-type strain, were further investigated by quantitative real-time PCR, revealing a very compact set of genes, as follows: norB (encoding NO reductase), dnrN (encoding a protein putatively involved in the repair of nitrosative damage to iron-sulfur clusters), aniA (encoding nitrite reductase), nirV (a putative nitrite reductase assembly protein), and mobA (a gene associated with molybdenum metabolism in other species but with a frame shift in N. meningitidis). In all cases, NsrR acts as a repressor. The NO protection systems norB and dnrN are regulated by NO in an NsrR-dependent manner, whereas the NO protection system cytochrome c' (encoded by cycP) is not controlled by NO or NsrR, indicating that N. meningitidis expresses both constitutive and inducible NO protection systems. In addition, we present evidence to show that the anaerobic response regulator FNR is also sensitive to NO but less so than NsrR, resulting in complex regulation of promoters such as aniA, which is controlled by both FNR and NsrR: aniA was found to be maximally induced by intermediate NO concentrations, consistent with a regulatory system that allows expression during denitrification (in which NO accumulates) but is down-regulated as NO approaches toxic concentrations.


Acrylamide: update on selected research activities conducted by the European food and drink industry.
This paper reviews the progress made by the European food and drink industry (CIAA) on acrylamide with regard to analytical methods, mechanisms of formation, and mitigation research in the major food categories. It is an update on the first CIAA review paper, "A Review of Acrylamide: An Industry Perspective on Research, Analysis, Formation and Control." Initial difficulties with the establishment of reliable analytical methods, in most cases, have now been overcome, but challenges remain in terms of the need to develop simple and rapid test methods and certified reference materials. Many trials have been conducted under laboratory and experimental conditions in a variety of foods, and a number of possible measures have been identified to relatively lower the amounts of acrylamide in food. Promising applications were studied in reconstituted potato models by addition of amino acids or use of asparaginase. In bakery wares, predictive models have been established to determine the role of ammonium carbonate and invert sugar in acrylamide formation. Studies in several commercial foods showed that acrylamide is not stable over time in roasted and ground coffee. Some progress in relatively lowering acrylamide in certain food categories has been achieved, but at this stage can only be considered marginal. Any options that are chosen to reduce acrylamide in commercial products must be technologically feasible and must not adversely affect the quality and safety of the final product.


Validation of ultrasonography in detecting structural disease of the urogenital tract of the koala, Phascolarctos cinereus.
A retrospective review of case records of ultrasonography and necropsy outcomes of 62 koalas was used to investigate the accuracy of ultrasonography in assessing koala urogenital tract structural disease at the Port Macquarie Koala Hospital. The results showed high concordance, supporting ultrasonography as an effective tool for evaluating structural disease of the koala urogenital tract, most commonly seen with chlamydiosis. The study also illustrates the advances benefiting animal welfare that can be made by wildlife carer groups through using a scientific, evidence-based approach.


Torsion of only spermatic cord in the absence of testis and/or epididymis results in contralateral testicular hypoxia.
Unilateral spermatic cord torsion in the presence or absence of ipsilateral testis causes hypoxia in the contralateral testis. An experimental study was conducted to find the most important structure that causes contralateral testicular hypoxia following ipsilateral twisting. In five groups each consisting of 10 rats sham operations, epididymoorchiectomy, spermatic cord torsion, spermatic cord torsion following subepididymal orchiectomy or spermatic cord torsion following epididymoorchiectomy were performed. Lactic acid, hypoxanthine and thiobarbituric acid reactive products of lipid peroxidation (TBAR) were determined in the contralateral testis. While lactic acid, hypoxanthine and TBAR values did not differ significantly following sham and epididymoorchiectomy procedures, evaluation of other groups revealed significantly increased values compared with sham and epididymoorchiectomy groups. Since torsion of only spermatic cord and testicular vasculature causes contralateral testicular hypoxia, testis and epididymis do not seem to be mandatory for occurrence of contralateral testicular hypoxia. Testicular artery under distress seems to be the most important structure that results in contralateral testicular hypoxia following torsion.


Coagulopathy and inhospital deaths in patients with acute subdural hematoma.
Acute subdural hematoma (SDH) is one of the most lethal forms of intracranial injury; several risk factors predictive of a worse outcome have been identified. Emerging research suggests that patients with coagulopathy and intracerebral hemorrhage have a worse outcome than patients without coagulopathy but with intracerebral hemorrhage. The authors sought to determine if such a relationship exists for patients with acute SDH. The authors conducted a retrospective analysis of consecutive patients admitted to a neurosciences intensive care unit with acute SDH over a 4-year period (January 1997-December 2001). Demographic data, laboratory values, admission source, prior functional status, medical comorbidities, treatments received, and discharge disposition were recorded, as were scores on the Acute Physiology, Age, and Chronic Health Evaluation III (APACHE III). Coagulopathy was defined as an internal normalized ratio>1.2 or a prothrombin time>or=12.7 seconds. Univariate and multivariate analyses were performed on 244 patients to determine factors associated with worse short-term outcomes. The authors identified 248 patients with acute SDH admitted to the neurointensive care unit during the study period, of which 244 had complete data. Most were male (61%), and the mean age of the study population was 71.3+/-15 years (range 20-95 years). Fifty-three patients (22%) had coagulopathy. The median APACHE III score was 43 (range 11-119). Twenty-nine patients (12%) died in the hospital. Independent predictors of inhospital death included APACHE III score (odds ratio [OR] 4.4, 95% confidence interval [CI] 1.4-13.4, p=0.011) and coagulopathy (OR 2.7, 95% CI 1.1-7.1, p=0.037). Surgical evacuation of acute SDH was associated with reduced inhospital deaths (OR 0.2, 95% CI 0.1-0.6, p=0.003). Coagulopathy is independently associated with inhospital death in patients with acute SDH. Time to treatment to correct coagulopathy using fresh frozen plasma and/or vitamin K was prolonged.


Long-term effects on cognitive function of postmenopausal hormone therapy prescribed to women aged 50 to 55 years.
Postmenopausal hormone therapy with conjugated equine estrogens (CEEs) may adversely affect older women's cognitive function. It is not known whether this extends to younger women. To test whether prescribing CEE-based hormone therapy to postmenopausal women aged 50 to 55 years has longer-term effects on cognitive function. Trained, masked staff assessed participants with an annual telephone-administered cognitive battery that included measures of global and domain-specific cognitive functions. Cognitive testing was conducted an average of 7.2 years after the trials ended, when women had a mean age of 67.2 years, and repeated 1 year later. Enrollment occurred from 1996 through 1999. Forty academic research centers. The study population comprised 1326 postmenopausal women, who had begun treatment in 2 randomized placebo-controlled clinical trials of hormone therapy when aged 50 to 55 years. The clinical trials in which the women had participated had compared 0.625 mg CEE with or without 2.5 mg medroxyprogesterone acetate over a mean of 7.0 years. The primary outcome was global cognitive function. Secondary outcomes were verbal memory, attention, executive function, verbal fluency, and working memory. Global cognitive function scores from women who had been assigned to CEE-based therapies were similar to those from women assigned to placebo: mean (95% CI) intervention effect of 0.02 (−0.08 to 0.12) standard deviation units (P = .66). Similarly, no overall differences were found for any individual cognitive domain (all P > .15). Prespecified subgroup analyses found some evidence that CEE-based therapies may have adversely affected verbal fluency among women who had prior hysterectomy or prior use of hormone therapy: mean treatment effects of −0.17 (−0.33 to −0.02) and −0.25 (−0.42 to −0.08), respectively; however, this may be a chance finding. CEE-based therapies produced no overall sustained benefit or risk to cognitive function when administered to postmenopausal women aged 50 to 55 years. We are not able to address whether initiating hormone therapy during menopause and maintaining therapy until any symptoms are passed affects cognitive function, either in the short or longer term. clinicaltrials.gov Identifier: NCT01124773.


OpenDeID Pipeline for Unstructured Electronic Health Record Text Notes Based on Rules and Transformers: Deidentification Algorithm Development and Validation Study.
Electronic health records (EHRs) in unstructured formats are valuable sources of information for research in both the clinical and biomedical domains. However, before such records can be used for research purposes, sensitive health information (SHI) must be removed in several cases to protect patient privacy. Rule-based and machine learning-based methods have been shown to be effective in deidentification. However, very few studies investigated the combination of transformer-based language models and rules. The objective of this study is to develop a hybrid deidentification pipeline for Australian EHR text notes using rules and transformers. The study also aims to investigate the impact of pretrained word embedding and transformer-based language models. In this study, we present a hybrid deidentification pipeline called OpenDeID, which is developed using an Australian multicenter EHR-based corpus called OpenDeID Corpus. The OpenDeID corpus consists of 2100 pathology reports with 38,414 SHI entities from 1833 patients. The OpenDeID pipeline incorporates a hybrid approach of associative rules, supervised deep learning, and pretrained language models. The OpenDeID achieved a best F1-score of 0.9659 by fine-tuning the Discharge Summary BioBERT model and incorporating various preprocessing and postprocessing rules. The OpenDeID pipeline has been deployed at a large tertiary teaching hospital and has processed over 8000 unstructured EHR text notes in real time. The OpenDeID pipeline is a hybrid deidentification pipeline to deidentify SHI entities in unstructured EHR text notes. The pipeline has been evaluated on a large multicenter corpus. External validation will be undertaken as part of our future work to evaluate the effectiveness of the OpenDeID pipeline.


Terahertz direct-contact refractometer/spectrometer.
A method for terahertz (THz) reflection spectroscopy is presented that utilizes direct contact between the backside of the pulsed emitter and the sample. Changes in the complex reflectivity of the emitter-sample interface are used to measure the spectrum. This method is especially useful for spectroscopy of liquid samples and soft materials. It simplifies the optical apparatus, has good sensitivity, and has capability for use in the construction of miniaturized THz probes. The problem of nonplanar wave fronts inside the emitter is discussed.


Percutaneous and limited open reduction of the articular surface of the distal radius.
Between 1979 and 1986, 40 patients with intraarticular fractures of the distal radius, in which anatomic reduction could not be obtained by closed manipulation or external fixation, underwent a combination of percutaneous and/or limited open reduction techniques to restore articular congruity. All 40 patients' radiographs that were retrospectively reviewed with an average follow-up of 4 years showed satisfactory extraarticular alignment in 85% of cases, and 37 patients (92.5%) demonstrated an articular step-off of less than or equal to 1 mm. Thirty-one patients retrieved for follow-up had a good functional result. The treatment goals of intraarticular fractures of the distal radius are anatomic restoration of the joint surface and optimal fixation to maintain reduction in an effort to prevent posttraumatic arthrosis of the wrist.


Chrysanthemum zawadskil Herbich attenuates dexamethasone-induced muscle atrophy through the regulation of proteostasis and mitochondrial function.
Chrysanthemum zawadskii Herbich (CZH) is used in traditional medicine to treat inflammatory diseases and diabetes. However, the effects of CZH on muscle wasting remains to be studied. Here, we investigated the effect of CZH on dexamethasone (DEX), a synthetic glucocorticoid, induced muscle atrophy. To examine the effect of CZH on muscle atrophy, C2C12 myotubes were co-treated with DEX and CZH for 24 h. The treatment with CZH prevented DEX-induced myotube atrophy in a dose-dependent manner. CZH inhibited the DEX-induced decrease of the MHC isoforms and the upregulation of atrogin-1 and MuRF1 in C2C12 differentiated cells. C57BL/6 mice were supplemented with 0.1 % CZH for 8 weeks, with DEX-induced muscle atrophy stimulated in the last 3 weeks. In the mice, CZH supplementation effectively reversed DEX-induced skeletal muscle atrophy and increased the exercise capacity of the mice through the inhibition of glucocorticoid receptor translocation. Additionally, we observed that DEX-evoked impaired proteostasis was ameliorated via the Akt/mTOR pathway. CZH also prevented the DEX-induced decrease in the mitochondrial respiration. HPLC analysis demonstrated the highest concentration of acacetin-7-O-β-d-rutinoside (AR) among 4 compounds. Moreover, AR, a functional compound of CZH, prevented DEX-evoked muscle atrophy. Thus, we suggest that CZH could be a potential therapeutic candidate against muscle atrophy and AR is the main functional compound of CZH.


Characterization of 'Candidatus Syngnamydia salmonis' (Chlamydiales, Simkaniaceae), a bacterium associated with epitheliocystis in Atlantic salmon (Salmo salar L.).
Two Chlamydiales have previously been found to infect Atlantic salmon (Salmo salar L.), Candidatus Piscichlamydia salmonis and Candidatus Clavichlamydia salmonicola. Both develop intracellularly in cyst-like inclusions in gill cells, generally referred to as epitheliocysts. Here, we present evidence for the association of a novel species of Chlamydiales with epitheliocystis in Atlantic salmon. Based on its partial 16S rRNA gene sequence, it is a new member of the family Simkaniaceae, and a 95.7 % identity to the type species Candidatus Syngnamydia venezia suggests inclusion in the candidate genus Syngnamydia. The presence of the bacterium in epitheliocysts in gills of Atlantic salmon was demonstrated by RNA-RNA hybridization. Ultrastructurally, the novel bacterium produces pleomorphic reticulate bodies and elementary bodies (EBs) with a characteristic morphology. The EBs are short rods with a terminal disc-like cap area, a sub-apical spherical vacuole-like electron-lucent structure and a post-equatorial nucleoid. We propose the name Candidatus Syngnamydia salmonis for this new agent from epitheliocysts in seawater-reared salmon .


Assessment of striatal & postural deformities in patients with Parkinson's disease.
Though striatal and postural deformities are known to occur commonly in atypical Parkinsonism patients, these may also be seen in patients with Parkinson's disease (PD). These are frequently misdiagnosed as joint or orthopaedic pathology leading to unnecessary investigations. This study was conducted to observe the various striatal and postural deformities among patients with PD in India. This study was conducted at a tertiary care teaching institute in north# India. Seventy consecutive patients with PD diagnosed as per the modified UK Brain Bank criteria were included. Various striatal (hand & foot) and postural (antecollis, camptocormia, scoliosis & Pisa syndrome) deformities and their relation with the duration of disease, severity [measured by the Unified Parkinson's Disease Rating Scale (UPDRS)] and levodopa intake were analyzed. Of the 70 patients with PD, 34 (48.57%) had either striatal or postural deformities. Striatal foot was the most common deformity observed (25.71%). Camptocormia was the second most common deformity (20%). Striatal and postural deformities were seen in more advanced PD as suggested by significantly higher UPDRS and Hoehn and Yahr scale (P<0.001). Striatal deformities were more ipsilateral to PD symptom onset side (agreement 94.44%). Pisa and scoliosis concavity were more on contralateral side to PD symptoms onset side (66.67%). Our results showed that striatal and postural deformities were common and present in about half of the patients with PD. These deformities we more common in patients with advanced stage of PD.


Mouse Resource Browser--a database of mouse databases.
The laboratory mouse has become the organism of choice for discovering gene function and unravelling pathogenetic mechanisms of human diseases through the application of various functional genomic approaches. The resulting deluge of data has led to the deployment of numerous online resources and the concomitant need for formalized experimental descriptions, data standardization, database interoperability and integration, a need that has yet to be met. We present here the Mouse Resource Browser (MRB), a database of mouse databases that indexes 217 publicly available mouse resources under 22 categories and uses a standardised database description framework (the CASIMIR DDF) to provide information on their controlled vocabularies (ontologies and minimum information standards), and technical information on programmatic access and data availability. Focusing on interoperability and integration, MRB offers automatic generation of downloadable and re-distributable SOAP application-programming interfaces for resources that provide direct database access. MRB aims to provide useful information to both bench scientists, who can easily navigate and find all mouse related resources in one place, and bioinformaticians, who will be provided with interoperable resources containing data which can be mined and integrated. Database URL: http://bioit.fleming.gr/mrb.


[Photodynamic therapy in dermatology: basic principles].
Photodynamic therapy involves the administration of a photosensitizing drug and its subsequent activation by light at wavelengths matching the absorption spectrum of the photosensitizer. Currently, topical photodynamic therapy has received approval for the treatment of cutaneous oncologic conditions such as actinic keratoses, Bowen's disease and superficial basal cell carcinoma in many countries in the world. Multicenter randomized controlled studies have demonstrated high efficacy and superior cosmetic outcome over standard therapies. For many non-oncologic dermatological diseases such as acne vulgaris, viral warts and localized scleroderma, case reports and small series have confirmed the potential of photodynamic therapy. After the development of topical photosensitizers 5-aminolevulinic acid (ALA) or its methyl ester (MAL), photodynamic therapy has gained worldwide popularity in dermatology, as these drugs do not induce prolonged phototoxicity as the systemic photosensitizing hematoporphyrin derivatives do. The production of reactive oxygen intermediates such as singlet oxygen depends on the concentration and localization of the photosensitizer in the diseased tissue as well as the applied light dose. Either incoherent lamps or LED arrays are suitable for the cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving inflammatory condition.


Definitions of the physical properties of pressure ulcers and characterisation of their regional variance.
A pressure ulcer is a localised injury of the skin and underlying tissue that usually develops over a bony prominence. A decrease in the pressure over the bony prominence effectively prevents pressure ulcers; however, no studies have systematically assessed the physical properties of existing pressure ulcers. To characterise pressure ulcers, we established new terminology that clarifies the physical properties of pressure ulcers: wound mobility was defined as movement using the bony prominence as a predefined specific marker, and wound deformity was defined as a change in the three-dimensional shape of the wound. Observational studies using this terminology showed that the distinct physical properties of pressure ulcers depend on the site of development and the wound depth according to the National Pressure Ulcer Advisory Panel criteria. Most grade IV sacrum pressure ulcers exhibited mobility and deformity. Superficial sacrum pressure ulcers below grade II showed only mobility. In contrast, foot pressure ulcers did not exhibit mobility or deformity. We propose a new concept, 'wound physical property', for understanding the unique pathogenesis of pressure ulcers.


Norepinephrine release during autoregulatory escape: effects of alpha 2-receptor blockade.
The partial recovery that intestinal blood flow undergoes during continued sympathetic nerve stimulation is termed autoregulatory escape. This study tested two hypotheses that might explain escape: 1) diminishing norepinephrine (NE) release during sustained stimulation and 2) an alpha 2-receptor-mediated competition between local and neural control mechanisms. The rates of NE release before and during stimulation of the perivascular sympathetic nerves were determined by measuring blood flow in isolated loops of canine small intestine and assaying the concentrations of NE in arterial and venous blood. The presence of functional alpha 2-receptors was demonstrated by clonidine injections, and the effects of alpha 2-receptor blockade were studied during yohimbine infusions. The time course of NE release was inconsistent with a cause-effect relationship; NE release was greatest during the phase when resistance had already escaped. Deliberately altering NE release by changing the stimulus duration did not affect escape. The study demonstrated 1) that diminished NE release during continued sympathetic stimulation does not occur and cannot account for escape, 2) that resistance vessels in the canine intestinal circulation possess functional alpha 2-receptors which are responsible for part of the vasoconstriction caused by sympathetic stimulation, 3) that blockade of presynaptic alpha 2-receptors significantly enhanced NE release during the initial 30-s period but not during the escape phase, and 4) that alpha 2-receptor blockade enhances autoregulatory escape. Altogether these findings indicate that the postsynaptic alpha 2-receptors on intestinal resistance vessels deserve further investigation as the possible site at which local and neural mechanisms compete to influence vascular resistance.


Preparation and anticoagulant activity of trimethylsilyl heparin in Carbowax.
Trimethylsilyl heparin, when administered intraduodenally or intragastrically to rats, did not increase intestinal absorption and, consequently, the clotting times were not influenced. However, suspension of sodium heparin in Carbowax 200 prolonged the whole blood clotting time at a dose of 50 mg/kg when given intraduodenally or intragastrically to rats.